| 1. |
- Genel, F, et al.
(author)
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Complement factor I deficiency associated with recurrent infections, vasculitis and immune complex glomerulonephritis
- 2005
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 37:8, s. 615-618
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Journal article (peer-reviewed)abstract
- Here we report complement factor I deficiency in an 11-y-old girl from a consanguineous Turkish family, who presented with recurrent pyogenic infections, vasculitic eruptions and immune complex glomerulonephritis. A moderately low C3 level together with the clinical picture suggested a deficiency affecting regulation of complement activation. Analysis of haemolytic activity revealed absence of alternative pathway activity and subsequent analysis showed no detectable factor I (<2%) together with a low level of factor B and a moderately low level of factor H, indicating consumption secondary to the factor I deficiency. Factor I inhibits complement activation beyond C3 by cleavage of C3b in the presence of cofactors. Complement factor I deficiency is frequently associated with recurrent pyogenic infections mainly affecting the upper and lower respiratory tract, or presenting as meningitis or septicaemia, while rheumatic disorders have not been a prominent feature. The patient's sister also suffered from recurrent pyogenic infections and had a low C3 level clearly suggesting the same deficiency.
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| 2. |
- Genel, Ferah, et al.
(author)
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Properdin deficiency in a boy with fulminant meningococcal septic shock
- 2006
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In: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 95:11, s. 1498-1500
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Journal article (peer-reviewed)abstract
- Bacterial meningitis is a rare presentation for congenital immunodeficiency, but meningococcal invasive diseases and meningitis have been associated with late complement component deficiencies and properdin deficiency. A 5(1)/(2)-y-old boy of non-consanguineous parents was admitted to our hospital with meningococcal septic shock. He had previously been suffering from recurrent respiratory infections. His 13-y-old brother had also been treated for meningococcal meningitis when he was 7 y old. Immunological studies, done after recovery, on the patient and his two brothers revealed normal immunoglobulin, IgG subclasses, C3, C4 and CH50 levels. Haemolytic activity of the alternative complement pathway could not be detected, and properdin concentrations were < 0.01 mg/l in serum samples from the patient and his brothers. The patient and family members received quadrivalent polysaccharide meningococcal vaccine. The patient was discharged on penicillin prophylaxis, and he remained healthy during the ensuing year. Conclusion: Our findings stress that measurement of the haemolytic activity of the alternative complement pathway in addition to classical pathway haemolytic complement activity should be performed in patients with meningococcal disease to reveal various forms of complement deficiency. This is particularly important when there is a family history, or recurrences or infection due to uncommon serogroups. Deficient individuals and affected family members might be protected from infection by vaccination.
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| 3. |
- Melander Skattum, Lillemor, et al.
(author)
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Antibodies against Four Proteins from a Streptococcus pyogenes Serotype M1 Strain and Levels of Circulating Mannan-Binding Lectin in Acute Poststreptococcal Glomerulonephritis.
- 2006
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 140:1, s. 9-19
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Journal article (peer-reviewed)abstract
- <i>Background:</i> Responses against antigens from the potentially nephritogenic <i>Streptococcus pyogenes</i> serotype M1 in patients with acute poststreptococcal glomerulonephritis (AGN) were studied to seek indications of expression of these antigens during the preceding infection. Also, the question was asked whether the complement protein mannan-binding lectin (MBL) is required for development of the hypocomplementemia associated with AGN. Hypothetically, the lectin pathway might trigger the alternative pathway, which is consistently activated in AGN. <i>Methods:</i> Antibodies against three proteins associated with M1, M1 protein, streptococcal inhibitor of complement (SIC) and protein H, an IgG-binding protein, were determined by ELISA in 56 children and 17 adults with AGN. Antibodies against streptococcal cysteine proteinase, which is produced by all serotypes of <i>S. pyogenes</i>, were also examined. MBL concentrations were measured in the same 71 patients by a sandwich ELISA. <i>Results:</i> Increased concentrations of antibodies were found against all four streptococcal proteins, albeit not uniformly distributed between different subgroups of patients. The prevalence of low MBL concentrations (<100 µg/l) including 2 patients with undetectable MBL (<10 µg/l) was similar in AGN (11%) and in controls (16%). <i>Conclusions:</i> Our results give evidence of exposure to SIC and protein H in conjunction with AGN. This implies that SIC and protein H and/or cross-reacting proteins may have a role in the pathogenesis of AGN or that streptococci expressing SIC or protein H are nephritogenic for other reasons. The finding of MBL-deficient individuals among the patients demonstrates that MBL is not necessary for the recruitment of complement in AGN.
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| 4. |
- Melander Skattum, Lillemor
(author)
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Complement aberrations and autoantibodies to complement proteins in relation to disease mechanisms.
- 2008
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Doctoral thesis (other academic/artistic)abstract
- The complement system, a part of the innate immune system with several links to the adaptive immune system, plays an important role in the pathogenesis of many diseases. The purpose of this thesis was to document and clarify some of these mechanisms. The thesis is based on four papers (I-IV). (I and II) Autoantibodies to the C3 cleaving enzyme complex of the alternative pathway, C3 nephritic factors (C3 NeF), cause partial C3 deficiency and are associated with increased susceptibility to bacterial infections. By analysis of samples from 20 patients with C3 NeF, it was confirmed that C3 NeF are of at least 2 types; one with fluid phase (C3 NeF type I) and one with solid phase (C3 NeF type II) activity. Different types of C3 NeF were associated with different serum complement profiles and symptoms. Only C3 NeF type II were found to be associated with circulating autoantibodies to the collagenous region of C1q (aC1qCLR). Defense against Neisseria meningitidis in 26 patients with low C3 concentrations due to C3 NeF was investigated. In patients and control children, homozygosity for the IgG1 and IgG3 IGHG alleles G1M*f and G3M*b was found to be associated with higher serum bactericidal activity (SBA) than was heterozygosity. IGHG alleles correlated to IgG subclass binding to live meningococci, while IgG subclass binding did not correlate to SBA. Thus, the mechanism of influence from IGHG genes on SBA is unclear. IGHG variants are important for immune defense against meningococci in states of deficient complement function. This relationship should be examined further. (III) Serum levels of mannan-binding lectin (MBL) and antibodies to proteins from a potentially nephritogenic Streptococcus pyogenes strain (serotype M1 strain AP1) were investigated in 73 patients with acute poststreptococcal glomerulonephritis (AGN). Antibody responses to the serotype M1-related antigens M1, protein H and streptococcal inhibitor of complement were increased in patients compared to controls. The presence of MBL deficient individuals (serum concentration <0.1 mg/L) among AGN patients showed that the lectin pathway is not required in the pathogenesis of AGN. (IV) Autoimmunity has been implied to participate in the pathogenesis of idiopathic sudden hearing loss (ISHL). Autoantibodies were analysed in sera from 92 patients with ISHL. The most frequently occurring antibody was aC1qCLR, detected in 12 patients (13 %), all with normal serum concentrations of C1q. In ISHL, aC1qCLR probably represents cross-reactivity between C1q and inner ear protein(s).
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| 5. |
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| 6. |
- Melander Skattum, Lillemor, et al.
(author)
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Serum bactericidal activity against Neisseria meningitidis in patients with C3 nephritic factors is dependent on IgG allotypes.
- 2008
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In: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 129, s. 123-131
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Journal article (peer-reviewed)abstract
- The main mechanisms of immune defense against Neisseria meningitidis are serum bactericidal activity (SBA) and opsonophagocytosis. Many complement deficiencies, among them acquired partial C3 deficiency due to stabilizing autoantibodies against the alternative pathway C3 convertase (C3 nephritic factors, C3 NeF); increase the risk of meningococcal infection. SBA against meningococci in patients with C3 NeF was determined along with allelic variants (GM alleles) of the immunoglobulin constant heavy G chain (IGHG) genes. In patients with C3 NeF and in control children, individuals homozygous for G1Mf and G3Mb showed higher SBA against meningococci than heterozygous individuals. Partial complement deficiency in early childhood might explain the influence of GM variants on SBA in control children. These novel findings imply that the IGHG genotype is important in defense against meningococci in individuals with low complement function and possibly in combination with other immunodeficiencies.
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